Universal Transcriptional Responses to Different Modalities of Traumatic Stress as a Measure of Stress Exposure

Molecular diagnostic tools that can robustly and quantitatively measure the response to traumatic stress would be of considerable value in assessing the individual risk of developing post-traumatic stress disorder or stress-induced depression following stress exposure. The gene regulatory network can integrate and encode a large number of different signals, including those elicited by exposure to stress. We find that many genes respond to at least one modality of stress but only a subset of stress-sensitive genes track stress exposure across multiple stress modalities and are thus universal markers of stress exposure. A sensitive and robust measure of stress exposure can be constructed using a small number of genes selected from this modality-independent set of stress-sensitive genes. This stress-sensitive gene expression (SSGE) index can detect chronic traumatic stress exposure in a wide range of different stress models in a manner that is relatively independent of the modality of stress exposure and that parallels the intensity of stress exposure in a dose-dependent manner.